Wettable hydrogels comprising reactive, hydrophilic, polymeric internal wetting agents

ABSTRACT

The present invention relates to wettable silicone hydrogels comprising the reaction product of at least one siloxane containing component and at least one reactive, hydrophilic polymeric internal wetting agent. The present invention further relates to silicone hydrogel contact lenses comprising at least one oxygen permeable component, and an amount of reactive, hydrophilic polymeric internal wetting agent sufficient to impart wettability to said device.

FIELD OF THE INVENTION

This invention relates to silicone hydrogels comprising at least onereactive, hydrophilic polymeric internal wetting agent, as well asmethods for their production and use.

BACKGROUND OF THE INVENTION

Contact lenses have been used commercially to improve vision since atleast the 1950s. The first contact lenses were made of hard materialsand as such were somewhat uncomfortable to users. Modern soft contactlenses are made of softer materials, typically hydrogels. Recently softcontact lenses made from silicone hydrogels have been introduced.Silicone hydrogels are water-swollen polymer networks that have highoxygen permeability. However, some users experience discomfort andexcessive ocular deposits leading to reduced visual acuity when usingthese lenses.

Others have tried to alleviate this problem by coating the surface ofsilicone hydrogel contact lenses with hydrophilic coatings, such asplasma coatings. For example, it has been disclosed that siliconehydrogel lenses can be made more compatible with ocular surfaces byapplying plasma coatings to the lens surface or by treating the surfacewith reactive hydrophilic polymers. Reactive functionalities on or nearthe surface of medical devices are chemically attached to reactivefunctional groups on a hydrophilic polymer, thereby creating ahydrophilic surface. In one example,Vinylpyrrolidone-co-4-vinylcyclohexyl-1,2-epoxide polymer was used tocoat a silicone substrate. However, surface modifications are usuallyadded steps in contact lens production.

Surface active macromonomers comprising 10-90% repeating units fromethylenically unsaturated hydrophobic monomer have been disclosed foruse in contact lens applications. A 2-step reaction is carried out toform a PVP-methacrylate. The total process involves several syntheticsteps and, as a result, requires extensive purification of eachintermediate. The resultant “surface-active macromonomers” are low inmolecular weight with Mn, Mw, and polydispersity values of 4,900, 8,900,and 1.8, respectively (versus PEG standards). The inclusion ofsubstantial quantities of hydrophobic monomers may prevent the formationof wettable contact lenses. Wettability data for lens wear longer thanone hour is not reported.

Incorporation of internal hydrophilic wetting agents into a macromercontaining reaction mixture has been disclosed. However, not allsilicone containing macromers display compatibility with hydrophilicpolymers. Modifying the surface of a polymeric article by addingpolymerizable surfactants to a monomer mix used to form the article hasalso been disclosed. However, lasting in vivo improvements inwettability and reductions in surface deposits are not likely.

Poly(N-vinyl-2-pyrrolidone) (PVP) or poly-2-ethyl-2-oxazoline have beenadded to hydrogel compositions to form interpenetrating networks whichshow a low degree of surface friction, a low dehydration rate and a highdegree of biodeposit resistance.

It has been previously shown that high molecular weight (Mw>300,000) PVPcan be entrapped within a cross-linked silicone hydrogel matrix.However, a small loss of the high molecular weight PVP (<10 weightpercent) is still observed during the extraction purification process inorganic solvents.

Therefore it would be advantageous to find additional hydrophilicpolymers which may be incorporated into a lens formulation to improvewettability of the lens without a surface treatment.

SUMMARY OF THE INVENTION

The present invention relates to reactive, hydrophilic polymericinternal wetting agents for use in biomedical devices.

The present invention further relates to a wettable silicone hydrogelcomprising the reaction product of at least one siloxane containingcomponent and at least one reactive, hydrophilic polymeric internalwetting agent.

The present invention further relates to silicone hydrogel contactlenses comprising at least one oxygen permeable component, and an amountof reactive, hydrophilic polymeric internal wetting agent sufficient toimpart wettability to said device.

DESCRIPTION OF THE FIGURES

FIG. 1 is a graph showing percent loss of reactive and non-reactivehydrophilic polymeric internal wetting agents.

FIG. 2 is a graph showing percent loss of reactive and non-reactivehydrophilic polymeric internal wetting agents.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, a “biomedical device” is any article that is designed tobe used while either in or on mammalian tissues or fluid, and preferablyin or on human tissue or fluids. Examples of these devices include butare not limited to catheters, implants, stents, and ophthalmic devicessuch as intraocular lenses and contact lenses. The preferred biomedicaldevices are ophthalmic devices, particularly contact lenses, mostparticularly contact lenses made from silicone hydrogels.

As used herein, the terms “lens” and “ophthalmic device” refer todevices that reside in or on the eye. These devices can provide opticalcorrection, wound care, drug delivery, diagnostic functionality,cosmetic enhancement or effect or a combination of these properties. Theterm lens includes but is not limited to soft contact lenses, hardcontact lenses, intraocular lenses, overlay lenses, ocular inserts, andoptical inserts.

As used herein, the phrase “without a surface treatment” means that theexterior surfaces of the devices of the present invention are notseparately treated to improve the wettability of the device. Treatmentswhich may be foregone because of the present invention include, plasmatreatments, grafting, coating and the like. However, coatings whichprovide properties other than improved wettability, such as, but notlimited to antimicrobial coatings and the application of color or othercosmetic enhancement may be applied to devices of the present invention.

As used herein the term “silicone containing compatibilizing component”means reaction components which contain at least one silicone and atleast one hydroxyl group. Such components have been disclosed in U.S.Ser. Nos. 10/236,538 and 10/236,762.

As used herein, “macromer” is a low molecular weight polymer having atleast one polymerizable end group and a degree of polymerization (DP)ranging from 10 to 1000 monomeric repeat units, which correspond to anumber average molecular weight range from approximately 100 toapproximately 100,000 Daltons.

As used herein the term “monomer” is a compound containing at least onepolymerizable group and an average molecular weight of about less than2000 Daltons, as measured via gel permeation chromatography usingrefractive index detection.

The compositions of the present invention comprise, consist essentiallyand consist of at least one silicone containing component and at leastone reactive, hydrophilic polymeric internal wetting agent. As usedherein, “reactive, hydrophilic polymeric internal wetting agent” refersto substances having a weight average molecular weight of at least about2000 Daltons, wherein said substances upon incorporation to siliconehydrogel formulations, improve the wettability of the cured siliconehydrogels. The reactive, hydrophilic polymeric internal wetting agentsmay have a wide range of molecular weights (weight average). Molecularweights of greater than about 5,000 Daltons; more preferably betweenabout 5,000 to about 2,000,000 Daltons are suitable. In some embodimentslower molecular weights from between about 5,000 to about 180,000Daltons, most preferably about 5,000 to about 150,000 Daltons may bepreferred, while in others higher molecular weight ranges, from about60,000 to about 2,000,000 Daltons, preferably between about 100,000 toabout 1,800,000 Daltons, more preferably about 180,000 to about1,500,000 Daltons and most preferably from about 180,000 to about1,000,000 (all weight average molecular weight) may be used.

The molecular weights for polymers having a molecular weight greaterthan about 2000 Daltons may be determined by gel permeationchromatography (GPC) {size exclusion chromatography (SEC)} usinghexafluoroisopropanol as solvent, and relate, unless otherwise stated,to poly(2-vinylpyridine) calibration standards.

The reactive, hydrophilic polymeric internal wetting agents (“IWAs”) ofthe present invention comprise at least 90% and preferably at leastabout 95% repeating units from hydrophilic components. As used herein ahydrophilic component is one which when polymerized with a small amountof crosslinking monomer, forms a polymer capable of absorbing at leastabout 5 wt % water, preferably more than about 10 wt % water, and insome cases more than about 20% water.

As used herein, “reactive” means any group that can undergo anionic,cationic or free radical polymerization. Free radical reactive groupsinclude acrylates, styryls, vinyls, vinyl ethers, C₁₋₆alkylacrylates,acrylamides, C₁₋₆alkylacrylamides, N-vinyllactams, N-vinylamides,C₂₋₁₂alkenyls, C₂₋₁₂alkenylphenyls, C₂₋₁₂alkenylnaphthyls, orC₂₋₆alkenylphenylC₁₋₆alkyls. Cationic reactive groups include vinylethers, epoxide groups and mixtures thereof. Preferred reactive groupsinclude methacrylates, acryloxys, methacrylamides, acrylamides, andmixtures thereof. The reactive, hydrophilic polymeric IWAs of thepresent invention may have one or more reactive group. In one embodimentthe reactive, hydrophilic, polymeric IWAs have one reactive group on aterminal end.

The reactive, hydrophilic polymeric internal wetting agents are presentin the formulations of these devices in an amount sufficient to providecontact lenses, which without surface modification remain substantiallyfree from surface depositions during use. Typical use periods include atleast about 8 hours, and preferably worn several days in a row, and morepreferably for 24 hours or more without removal. Substantially free fromsurface deposition means that, when viewed with a slit lamp, at leastabout 80 percent and preferably at least about 90 percent, and morepreferably about 100 percent of the lenses worn in the patientpopulation display depositions rated as none or slight, over the wearperiod.

Suitable amounts of reactive, hydrophilic polymeric internal wettingagent include from about 1 to about 15 weight percent, more preferablyabout 3 to about 15 percent, most preferably about 5 to about 12percent, all based upon the total weight of all reactive components.

Examples of reactive, hydrophilic polymeric internal wetting agentsinclude but are not limited to reactive, hydrophilic polymers derivedfrom polyamides, polylactones, polyimides, polylactams andfunctionalized polyamides, polylactones, polyimides, polylactams, suchas N,N-dimethyl acrylamide (DMA) functionalized by initiating thepolymerization of DMA with a lesser molar amount of ahydroxyl-functionalized azo initiator (such as, for example,2,2′-Azobis{2-[1-(2-hydroxyethyl)-2-imidazolin-2-yl]propane}dihydrochloride,2,2′-Azobis{2-methyl-N-[1,1-bis(hydroxymethyl)-2-hydroxyethyl]propionamide,2,2′-Azobis[2-methyl-N-(2-hydroxyethyl)propionamide], or 2,2′-Azobis{2-methyl-N-[2-(1-hydroxybutyl)]propionamide}) and then reacting thehydroxyl groups of the resulting hydrophilic polymer with materialscontaining radical polymerizable compounds, such as, but not limited to2-isocyanatoethyl methacrylate, methacrylic anhydride,3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate or methacryloylchloride to form the reactive, hydrophilic polymeric IWA. In oneembodiment, the reactive, hydrophilic polymeric internal wetting agentscomprise N groups either in the polymer backbone, in pendant groups, orboth. The reactive hydrophilic polymeric IWA may comprise DMA,oxazolines or N-vinyl pyrrolidone and can be treated with glycidylmethacrylate as an end-capping reagent. The glycidyl methacrylate groupscan be ring-opened to give hydroxyl groups that may be used inconjunction with another hydrophilic prepolymer in a mixed system toincrease the compatibility of the reactive, hydrophilic polymeric IWA,and any other groups that impart compatibility. Examples of the abovecompounds include hydrophilic polymers of Formulae I and reactive,hydrophilic polymeric internal wetting agents of Formulae II

In another example, reactive, hydrophilic polymeric IWAs can be made byinitiating the polymerization of a monomer (such as, for example, DMA)with a lesser molar amount of an amine-functionalized azo initiator(such as, for example, 2,2′-Azobis(2-methylpropionamide)dihydrochloride)and then reacting the amine groups of the resulting low molecular weightpolymers with materials containing free radical polymerizable groups,such as 2-isocyanatoethyl methacrylate, 3-isopropenyl-alpha,alpha-dimethylbenzyl isocyanate, methacrylic anhydride, acrylic acid,methacrylic acid, acryloyl chloride, or methacryloyl chloride. Examplesof the above compounds include low molecular weight hydrophilic polymersof Formulae III and reactive, hydrophilic polymeric IWAs of Formulae IV.

In yet a further example, reactive, hydrophilic polymeric IWAs can alsobe made by initiating the polymerization of a monomer (such as, forexample, DMA) with a lesser molar amount of a carboxylicacid-functionalized azo initiator (such as, for example,2,2′-Azobis[N-(2-carboxyethyl)-2-methylpropionamidine]tetrahydrate) andthen reacting the carboxylic acid groups of the resulting low molecularweight hydrophilic polymer with materials containing free radicalpolymerizable groups, such as, for example, 2-aminoethyl methacrylate or3-aminopropyl methacrylamide.

A person skilled in the art will recognize that incomplete reactionbetween the low molecular weight hydrophilic polymer and the freeradical polymerizable compound results in a mixture of products whichinclude, in part, the starting low molecular weight hydrophilic polymer,the reactive hydrophilic polymeric IWA, and unreacted free radicalpolymerizable compounds. If low molecular weight hydrophilic polymer ispresent in the final product mixture, it is not essential to remove itfrom the product mixture. Instead, the low molecular weight hydrophilicpolymer may remain, serve as a diluent in the contact lens formulationand be removed later during the purification of the lenses. Those ofskill in the art will also recognize that molecular weights of thereactive, hydrophilic polymeric IWAs will vary depending on the reactionparameters, such as amount of initiator present, reaction temperature,and monomer concentration. In addition, the presence of chain transferagents such thioglycolic acid and thiolactic acid can also be used tocontrol the molecular weights of the reactive, hydrophilic polymericIWAs.

Examples of the above compounds include low molecular weight hydrophilicpolymers of Formulae V and reactive, hydrophilic polymeric internalwetting agents of Formulae VI and VII.

One preferred class of reactive, hydrophilic polymeric IWAs includethose that contain a cyclic moiety in their backbone, more preferably, acyclic amide or cyclic imide. Reactive, hydrophilic polymeric IWAsinclude but are not limited to macromers derived from poly-N-vinylpyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam,poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone,poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam,poly-N-vinyl-3-ethyl-2-pyrrolidone, andpoly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole,poly-N-N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid,polyethylene oxide, poly-2-(ethyl-oxazoline), heparin polysaccharides,polysaccharides, mixtures and copolymers (including block or random,branched, multichain, comb-shaped or star shaped) thereof wherepoly-N-vinylpyrrolidone (PVP) is particularly preferred. Copolymersmight also be used such as graft copolymers of PVP. These lactamcontaining polymers may also be made reactive by treatment with alkaliand transition metal borohydrides, such as sodium borohydride (NaBH₄),zinc borohydride, sodium triacetoxyborohydride, bis(isopropoxytitanium)borohydride in solution, followed by reaction with suitablepolymerizable groups.

Another class of preferred reactive, hydrophilic polymeric IWAs includereactive polymers and copolymers comprising pendant acyclic amide groupscapable of association with hydroxyl groups.

Examples of suitable reactive, hydrophilic polymeric IWAs includepolymers and copolymers comprising, in the backbone, repeating units ofFormula VIII

Wherein Q is a direct bond,

wherein R^(c) is a C1 to C3 alkyl group;

R^(a) is selected from H, straight or branched, substituted orunsubstituted C1 to C4 alkyl groups,

R^(b) is selected from H, straight or branched, substituted orunsubstituted C1 to C4 alkyl groups, amino groups having up to twocarbons, amide groups having up to 4 carbon atoms and alkoxy groupshaving up to two carbons and wherein the number of carbon atoms in R^(a)and R^(b) taken together is 8, preferably 6 or less. As used hereinsubstituted alkyl groups include alkyl groups substituted with an amine,amide, ether or carboxy group.

In one preferred embodiment R^(a) and R^(b) are independently selectedfrom H, and substituted or unsubstituted C1 to C2 alkyl groups andpreferably unsubstituted C1 to C2 alkyl groups.

In another preferred embodiment Q is a direct bond, R^(a) and R^(b) areindependently selected from H, substituted or unsubstituted C1 to C2alkyl groups.

Preferably the reactive, hydrophilic polymeric IWAs of the presentinvention comprise a majority of the repeating unit of Formula VIII, andmore preferably at least about 80 mole % of the repeating unit ofFormula VIII.

Specific examples of repeating units of Formula VIII include repeatingunits derived from N-vinyl-N-methylacetamide, N-vinylacetamide,N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide,N-vinyl-2-methylpropionamide, N-vinyl-N,N′-dimethylurea, and thefollowing acyclic polyamides:

Additional repeating units may be formed from monomers selected fromN-vinyl amides, acrylamides, hydroxyalkyl (meth) acrylates, alkyl(meth)acrylates or other hydrophilic monomers and siloxane substitutedacrylates or methacrylates. Specific examples of monomers which may beused to form reactive, hydrophilic polymeric IWAs include asN-vinylpyrrolidone, N,N-dimethylacrylamide, 2-hydroxyethylmethacrylate,vinyl acetate, acrylonitrile, methyl methacrylate, hydroxypropylmethacrylate, 2-hydroxyethyl acrylate, and butyl methacrylate,methacryloxypropyl tristrimethylsiloxysilane and the like and mixturesthereof. Preferred additional repeating units monomers include ofN-vinylpyrrolidone, N,N-dimethylacrylamide, 2-hydroxyethylmethacrylateand mixtures thereof.

In one embodiment the reactive, hydrophilic polymeric IWA comprisespoly(N-vinyl-N-methylacetamide).

In yet another embodiment the reactive, hydrophilic polymeric IWAcomprises a reactive high molecular weight copolymer derived frommonomers comprising vinyllactam monomers and vinyl carboxylate monomers.Preferably the reactive high molecular weight copolymers have molecularweights (weight average) of at least about 60,000 Daltons, morepreferably between about 60,000 to about 750,000 Daltons, morepreferably still between about 100,000 to about 600,000 Daltons, andmost preferably between about 180,000 to about 500,000 Daltons.

In one embodiment these reactive high molecular weight copolymers may besynthesized in 3 steps. In the first step, a vinyllactam monomer and avinyl carboxylate monomer are copolymerized using a free radicalinitiator, resulting in a high molecular weight hydrophilic copolymer.In the second step, the carboxylate groups of the resultant copolymerare partially or completely hydrolyzed under appropriate reactionconditions, resulting in a “modified” high molecular weight copolymerthat is capable of further reacting with one or more photo-polymerizablecompounds via hydroxyl groups on the polymer backbone. Partialhydrolysis gives terpolymers comprising the units vinyllactam, vinylalcohol, and vinyl carboxylate, for example a terpolymer ofvinylpyrrolidone, vinyl acetate, and vinyl alcohol. In the third step,the modified high molecular weight hydrophilic copolymer is treated witha reactive group, as defined above, to generate the reactive,hydrophilic polymeric IWA.

Suitable N-vinyllactams include N-vinyl-2-pyrrolidone,N-vinyl-2-piperidone, N-vinyl-2-caprolactam,N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-3-methyl-2-piperidone,N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-pyrrolidone,N-vinyl-4-methyl-2-caprolactam, N-vinyl-5-methyl-2-pyrrolidone,N-vinyl-5-methyl-2-piperidone, N-vinyl-5,5-dimethyl-2-pyrrolidone,N-vinyl-3,3,5-trimethyl-2-pyrrolidone,N-vinyl-5-methyl-5-ethyl-2-pyrrolidone,N-vinyl-3,4,5-trimethyl-3-ethyl-2-pyrrolidone,N-vinyl-6-methyl-2-piperidone, N-vinyl-6-ethyl-2-piperidone,N-vinyl-3,5-dimethyl-2-piperidone, N-vinyl-4,4-dimethyl-2-piperidone,N-vinyl-7-methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam,N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl4,6-dimethyl-2-caprolactam,N-vinyl-3,5,7-trimethyl-2-caprolactam, N-vinylmaleimide,vinylsuccinimide, mixtures thereof and the like.

Preferred vinyllactams include heterocyclic monomers containing 4 carbonatoms in the heterocyclic ring. A highly preferred vinyllactam isN-vinyl-2-pyrrolidone.

Suitable vinyl carboxylate include compounds having both vinyl andcarboxylate functionality, preferably having up to 10 carbon atoms.Specific examples of suitable vinyl carboxylates include vinylheptanoate, vinyl hexanoate, vinyl pentanoate, vinyl butanoate, vinylpropanoate (vinyl propionate), vinyl ethanoate (vinyl acetate), vinyltrifluoroacetate, mixtures thereof and the like. A preferred vinylcarboxylate is vinyl acetate.

The high molecular weight copolymers may further comprise repeat unitsderived from vinyl alcohols. Suitable vinyl alcohols include2-hydroxyethyl 2-methyl-2-propenoate, p-hydroxystyrene, 4-vinylbenzylalcohol, diethylene glycol monomethacrylate,2-[2-(2-hydroxyethoxy)ethoxy]ethyl 2-methyl-2-propenoate,2,3-Dihydroxypropyl methacrylate, 2-hydroxy-1-(hydroxymethyl)ethyl2-methyl-2-propenoate, 2-hydroxyethyl acrylate, 2-hydroxypropylacrylate, butanediol monoacrylate, butanediol monomethacrylate,3-[(4-ethenylphenyl)methoxy]-1,2-propanediol,3-(ethenylphenyl)methoxy-1,2-propanediol mix of m-and p-isomers,2-(ethenylphenyl)methoxyacetic acid mixture of m- and p-isomers, xylitol1-methacrylate and xylitol 3-methacrylate, N-2-hydroxyethylmethacrylamide, N-2-hydroxyethyl acrylamide.

A class of reactive, hydrophilic polymeric IWAs of this embodimentcomprise units in their polymer chain derived from the following monomerunits (all numbers are preceded by the word “about”): Concentration(mole %) vinyl vinyl Reactive Vinyllactam alcohol carboxylate group85-99.9 0.1-15 0-15 0.1-15 85-99 0.1-10 0-10 0.1-10 85-99 0.1-10 0-50.1-5

The reactive, hydrophilic polymeric IWAs formed from high molecularweight copolymers may also be formed from copolymers derived frompolyamides, polylactones, polyimides, polylactams and functionalizedpolyamides, polylactones, polyimides, polylactams, polycarboxylates,such as N-vinyl-2-pyrrolidone (NVP) and vinyl acetate (VA)functionalized by initiating the polymerization of NVP and VA with alesser molar amount of an azo initiator, hydrolyzing or partiallyhydrolyzing the carboxylate groups, and then reacting the hydroxylgroups of the resulting high molecular weight hydrophilic copolymer withmaterials containing radical polymerizable groups, such as2-isocyanatoethyl methacrylate, methacrylic anhydride, acryloylchloride, or methacryloyl chloride to form the high molecular weightphoto-polymerizable hydrophilic copolymer (HMWPPHC). Suitable azocatalysts are known in the art and include AIBN,2,2′-azobis{2-[1-(2-hydroxyethyl)-2-imidazolin-2-yl]propane}dihydrochloride,2,2′-azobis{2-methyl-N-[1,1-bis(hydroxymethyl)-2-hydroxyethyl]propionamide,2,2′-azobis[2-methyl-N-(2-hydroxyethyl)propionamide}, 2,2′-azobis{2-methyl-N-[2-(1-hydroxybutyl)]propionamide},2,2′-azobis(2-methylpropionamide)dihydrochloride, or2,2′-azobis[N-(2-carboxyethyl)-2-methylpropionamidine]tetrahydrate).Reactive, hydrophilic polymeric IWAs made with glycidyl methacrylate mayalso be used. The glycidyl methacrylate ring can be opened to give adiol that may be used in conjunction with another hydrophilic polymer ina mixed system to increase the compatibility of the reactive,hydrophilic polymeric IWAs, compatibilizing components and any othergroups that impart compatibility. Examples of the above describedreactive, hydrophilic polymeric IWAs include compounds Formulae IX and X

The reactive, hydrophilic polymeric IWAs may be used in amounts fromabout 1 to about 15 weight percent, more preferably about 3 to about 15percent, most preferably about 5 to about 12 percent, all based upon thetotal of all reactive components.

In some embodiments it is preferred that the reactive, hydrophilicpolymeric IWA be soluble in the diluent at processing temperatures.Manufacturing processes that use water or water-soluble diluents may bepreferred due to their simplicity and reduced cost. In these embodimentsreactive, hydrophilic polymeric IWAs that are water soluble atprocessing temperatures are preferred.

In addition to the reactive, hydrophilic polymeric IWAs, the hydrogelsof the present invention further comprise one or moresilicone-containing components and, optionally one or more hydrophiliccomponents. The silicone-containing and hydrophilic components used tomake the polymer of this invention can be any of the known componentsused in the prior art to make silicone hydrogels. These termssilicone-containing component and hydrophilic component are not mutuallyexclusive, in that, the silicone-containing component can be somewhathydrophilic and the hydrophilic component can comprise some silicone,because the silicone-containing component can have hydrophilic groupsand the hydrophilic components can have silicone groups.

Further, silicone-containing component(s) and hydrophilic component(s)can be reacted prior to polymerization to form a prepolymer which islater polymerized in the presence of a diluent to form the polymer ofthis invention. When prepolymers or macromers are used, it is preferredto polymerize at least one silicone-containing monomer and at least onehydrophilic monomer in the presence of the diluent, wherein thesilicone-containing monomers and the hydrophilic monomers differ. Theterm “monomer” used herein refers to low molecular weight compounds(i.e. typically having number average molecular weights less than 700)that can be polymerized. Thus, it is understood that the terms“silicone-containing components” and “hydrophilic components” includemonomers, macromonomers and prepolymers.

A silicone-containing component is one that contains at least one[—Si—O—Si] group, in a monomer, macromer or prepolymer. Preferably, theSi and attached O are present in the silicone-containing component in anamount greater than 20 weight percent, and more preferably greater than30 weight percent of the total molecular weight of thesilicone-containing component. Useful silicone-containing componentspreferably comprise polymerizable functional groups such as acrylate,methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinylamide,and styryl functional groups. Examples of silicone-containing componentswhich are useful in this invention may be found in U.S. Pat. Nos.3,808,178; 4,120,570; 4,136,250; 4,153,641; 4,740,533; 5,034,461 and5,070,215, and EP080539. All of the patents cited herein are herebyincorporated in their entireties by reference. These references disclosemany examples of olefinic silicone-containing components.

Further examples of suitable silicone-containing monomers arepolysiloxanylalkyl(meth)acrylic monomers represented by the followingformula:

wherein: Z denotes H or lower alkyl and preferably H or methyl; Xdenotes O or NR⁴; each R⁴ independently denotes hydrogen or methyl,

each R¹-R³ independently denotes a lower alkyl radical or a phenylradical, and

j is 1 or 3 to 10.

Examples of these polysiloxanylalkyl (meth)acrylic monomers includemethacryloxypropyl tris(trimethylsiloxy) silane, pentamethyldisiloxanylmethylmethacrylate, and methyldi(trimethylsiloxy)methacryloxymethylsilane. Methacryloxypropyl tris(trimethylsiloxy)silane is the mostpreferred.

One preferred class of silicone-containing components is apoly(organosiloxane) prepolymer represented by Formula XII:

wherein each A independently denotes an activated unsaturated group,such as an ester or amide of an acrylic or a methacrylic acid or analkyl or aryl group (providing that at least one A comprises anactivated unsaturated group capable of undergoing radicalpolymerization); each of R⁵, R⁶, R⁷ and R⁸ are independently selectedfrom the group consisting of a monovalent hydrocarbon radical or ahalogen substituted monovalent hydrocarbon radical having 1 to 18 carbonatoms which may have ether linkages between carbon atoms;

R⁹ denotes a divalent hydrocarbon radical having from 1 to 22 carbonatoms, and

m is 0 or an integer greater than or equal to 1, and preferable 5 to400, and more preferably 10 to 300. One specific example isα,ω-bismethacryloxypropyl poly-dimethylsiloxane. Another preferredexample is mPDMS (monomethacryloxypropyl terminated mono-n-butylterminated polydimethylsiloxane).

Another useful class of silicone containing components includessilicone-containing vinyl carbonate or vinyl carbamate monomers of thefollowing formula:

wherein: Y denotes O, S or NH; R^(Si) denotes a silicone-containingorganic radical; R denotes hydrogen or lower alkyl, and preferably H ormethyl; d is 1, 2, 3 or 4; and q is 0 or 1. Suitable silicone-containingorganic radicals R^(Si) include the following:

wherein:

-   -   R¹⁰ denotes

Wherein p is 1 to 6; or an alkyl radical or a fluoroalkyl radical having1 to 6 carbon atoms; e is 1 to 200; q is 1, 2, 3 or 4; and s is 0, 1, 2,3, 4 or 5.

The silicone-containing vinyl carbonate or vinyl carbamate monomersspecifically include:1,3-bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyl-isiloxane3-(vinyloxycarbonylthio) propyl-[tris (trimethylsiloxysilane];3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)wilyl]propyl vinyl carbamate;trimethylsilylethyl vinyl carbonate; trimethylsilylmethyl vinylcarbonate, and

Another class of silicone-containing components includes compounds ofthe following formulae:(*D*A*D*G)_(a) *D*D*E¹;E(*D*G*D*A)_(a) *D*G*D*E¹ or;E(*D*A*D*G)_(a) *D*A*D*E¹  Formulae XIV-XVwherein:

D denotes an alkyl diradical, an alkyl cycloalkyl diradical, acycloalkyl diradical, an aryl diradical or an alkylaryl diradical having6 to 30 carbon atoms,

G denotes an alkyl diradical, a cycloalkyl diradical, an alkylcycloalkyl diradical, an aryl diradical or an alkylaryl diradical having1 to 40 carbon atoms and which may contain ether, thio or amine linkagesin the main chain;

* denotes a urethane or ureido linkage;

_(a) is at least 1;

A denotes a divalent polymeric radical of formula:

R¹¹ independently denotes an alkyl or fluoro-substituted alkyl grouphaving 1 to 10 carbon atoms which may contain ether linkages betweencarbon atoms; r is at least 1; and p provides a moiety weight of 400 to10,000; each of E and E¹ independently denotes a polymerizableunsaturated organic radical represented by formula:

wherein: R¹² is hydrogen or methyl; R¹³ is hydrogen, an alkyl radicalhaving 1 to 6 carbon atoms, or a —CO—Y—R¹⁵ radical wherein Y is —O—,Y—S— or —NH—; R¹⁴ is a divalent radical having 1 to 12 carbon atoms; Xdenotes —CO— or —OCO—; Z denotes —O— or —NH—; Ar denotes an aromaticradical having 6 to 30 carbon atoms; a is 0 to 6; b is 0 or 1; e is 0 or1; and c is 0 or 1.

A preferred silicone-containing component is represented by thefollowing formula:

wherein R¹⁶ is a diradical of a diisocyanate after removal of theisocyanate group, such as the diradical of isophorone diisocyanate.Another preferred silicone containing macromer is compound of formula X(in which x+y is a number in the range of 10 to 30) formed by thereaction of fluoroether, hydroxy-terminated polydimethylsiloxane,isophorone diisocyanate and isocyanatoethylmethacrylate.

Other silicone-containing components suitable for use in this inventioninclude those described is WO 96/31792 such as macromers containingpolysiloxane, polyalkylene ether, diisocyanate, polyfluorinatedhydrocarbon, polyfluorinated ether and polysaccharide groups. U.S. Pat.Nos. 5,321,108; 5,387,662 and 5,539,016 describe polysiloxanes with apolar fluorinated graft or side group having a hydrogen atom attached toa terminal difluoro-substituted carbon atom. Such polysiloxanes can alsobe used as the silicone monomer in this invention.

The hydrogels may further comprise hydrophilic components, such as thosewhich are capable of providing at least about 20% and preferably atleast about 25% water content to the resulting lens when combined withthe remaining reactive components. When present, suitable hydrophiliccomponents may be present in amounts up to about 60 weight %, preferablybetween about 10 to about 60 weight %, more preferably between about 15to about 50 weight % and more preferably still between about 20 to about40 weight %, all based upon the weight of all reactive components. Thehydrophilic monomers that may be used to make the polymers of thisinvention have at least one polymerizable double bond and at least onehydrophilic functional group. Examples of functional groups withpolymerizable double bonds include acrylic, methacrylic, acrylamido,methacrylamido, fumaric, maleic, styryl, isopropenylphenyl,O-vinylcarbonate, O-vinylcarbamate, allylic, O-vinylacetyl andN-vinyllactam and N-vinylamido double bonds. Such hydrophilic monomersmay themselves be used as crosslinking agents. “Acrylic-type” or“acrylic-containing” monomers are those monomers containing the acrylicgroup (CR′H══CRCOX)

wherein R is H or CH₃, R′ is H, alkyl or carbonyl, and X is O or N,which are also known to polymerize readily, such asN,N-dimethylacrylamide (DMA), 2-hydroxyethyl acrylate, glycerolmethacrylate, 2-hydroxyethyl methacrylamide, polyethyleneglycolmonomethacrylate, methacrylic acid, acrylic acid and mixtures thereof.

Hydrophilic vinyl-containing monomers which may be incorporated into thehydrogels of the present invention include monomers such as N-vinyllactams (e.g. N-vinyl pyrrolidone (NVP)), N-vinyl-N-methyl acetamide,N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide,N-2-hydroxyethyl vinyl carbamate, N-carboxy-β-alanine N-vinyl ester,with NVP being preferred.

Other hydrophilic monomers that can be employed in the invention includepolyoxyethylene polyols having one or more of the terminal hydroxylgroups replaced with a functional group containing a polymerizabledouble bond. Examples include polyethylene glycol with one or more ofthe terminal hydroxyl groups replaced with a functional group containinga polymerizable double bond. Examples include polyethylene glycolreacted with one or more molar equivalents of an end-capping group suchas isocyanatoethyl methacrylate (“IEM”), methacrylic anhydride,methacryloyl chloride, vinylbenzoyl chloride, or the like, to produce apolyethylene polyol having one or more terminal polymerizable olefinicgroups bonded to the polyethylene polyol through linking moieties suchas carbamate or ester groups.

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

More preferred hydrophilic monomers which may be incorporated into thepolymer of the present invention include hydrophilic monomers such asN,N-dimethyl acrylamide (DMA), 2-hydroxyethyl acrylate, glycerolmethacrylate, 2-hydroxyethyl methacrylamide, N-vinylpyrrolidone (NVP),and polyethyleneglycol monomethacrylate.

Most preferred hydrophilic monomers include DMA, NVP and mixturesthereof.

When the reactive, hydrophilic polymeric IWAs of the present inventionare incorporated into a silicone hydrogel formulation, it may bedesirable to include at least one a hydroxyl containing component tohelp compatibilize the reactive, hydrophilic polymeric IWA of thepresent invention and the silicone containing components. The hydroxylcontaining component that may be used to make the polymers of thisinvention have at least one polymerizable double bond and at least onehydrophilic functional group. Examples of polymerizable double bondsinclude acrylic, methacrylic, acrylamido, methacrylamido, fumaric,maleic, styryl, isopropenylphenyl, O-vinylcarbonate, O-vinylcarbamate,allylic, O-vinylacetyl and N-vinyllactam and N-vinylamido double bonds.The hydroxyl containing component may also act as a crosslinking agent.In addition the hydroxyl containing component comprises a hydroxylgroup. This hydroxyl group may be a primary, secondary or tertiaryalcohol group, and may be located on an alkyl or aryl group. Examples ofhydroxyl containing monomers that may be used include but are notlimited to 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate,2-hydroxyethyl methacrylamide, 2-hydroxyethyl acrylamide,N-2-hydroxyethyl vinyl carbamate, 2-hydroxyethyl vinyl carbonate,2-hydroxypropyl methacrylate, hydroxyhexyl methacrylate, hydroxyoctylmethacrylate and other hydroxyl functional monomers as disclosed in U.S.Pat. Nos. 5,006,622; 5,070,215; 5,256,751 and 5,311,223. Preferredhydroxyl containining monomers include 2-hydroxyethyl methacrylate, andhydroxyl functional monomers including silicone or siloxanefunctionalities, such as the hydroxyl-functionalized silicone containingmonomers disclosed in WO03/022321, and the compatibilizing componentscomprising at least one active hydrogen and at least one siloxane groupas disclosed in WO03/022322, the disclosure of which is incorporatedherein by reference. Specific examples of include 2-propenoic acid,2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disiloxanyl]propoxy]propylester (which can also be named(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane),3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane,bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane,3-methacryloxy-2-(2-hydroxyethoxy)propyloxy)propylbis(trimethylsiloxy)methylsilane,N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate andN,N,N′,N′-tetrakis(3-methacryloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxaneand mixtures thereof. include 2-hydroxyethyl methacrylate,3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane),3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane andmixtures thereof are preferred.

When a compatibilizing component is used, effective amounts ofcompatibilizing component in the polymer formulation include about 5percent (weight percent, based on the total weight of the reactivecomponents) to about 90 percent, preferably about 10 percent to about 80percent, most preferably, about 20 percent to about 50 percent.

Alternatively the reactive, hydrophilic polymeric IWAs may be includedin hydrophilic hydrogels. Generally these hydrogels are made from thehydrophilic monomers listed above. Commercially available hydrogelformulations include, but are not limited to etafilcon, polymacon,vifilcon, genfilcon A and lenefilcon A.

Generally the reactive components are mixed in a diluent to form areaction mixture. Suitable diluents are known in the art.

Classes of suitable diluents for silicone hydrogel reaction mixturesinclude ethers, esters, alkanes, alkyl halides, silanes, amides,alcohols and combinations thereof. Amides and alcohols are preferreddiluents with alcohols having 2 to 20 carbons, amides having 10 to 20carbon atoms derived from primary amines and carboxylic acids having 8to 20 carbon atoms. In some embodiments primary and tertiary alcoholsare preferred. Preferred classes include alcohols having 5 to 20 carbonsand carboxylic acids having 10 to 20 carbon atoms.

Specific diluents which may be used include 1-ethoxy-2-propanol,diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol,1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol,2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol,2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol,ethanol, 2-ethyl-1-butanol, SiGMA acetate, 1-tert-butoxy-2-propanol,3,3-dimethyl-2-butanol, tert-butoxyethanol, 2-octyl-1-dodecanol,decanoic acid, octanoic acid, dodecanoic acid,2-(diisopropylamino)ethanol mixtures thereof and the like.

Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol,1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol,3-methyl-3-pentanol, 2-pentanol, t-amyl alcohol, tert-butanol,2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol,3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoicacid, dodecanoic acid, mixtures thereof and the like.

More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol,1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol,1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, tert-amylalcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol,2-ethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, mixturesthereof and the like.

Suitable diluents for non-silicone containing reaction mixtures includeglycerin, ethylene glycol, ethanol, methanol, ethyl acetate, methylenechloride, polyethylene glycol, polypropylene glycol, low molecularweight PVP, such as disclosed in U.S. Pat. No. 4,018,853, U.S. Pat. No.4,680,336 and U.S. Pat. No. 5,039,459, including, but not limited toboric acid esters of dihydric alcohols, combinations thereof and thelike.

Mixtures of diluents may be used. The diluents may be used in amounts upto about 50% by weight of the total of all components in the reactionmixture. More preferably the diluent is used in amounts less than about45% and more preferably in amounts between about 15 and about 40% byweight of the total of all components in the reaction mixture.

In another embodiment, the diluent comprises a low molecular weighthydrophilic polymer without photo-polymerizable reactive groups. Thediluent may also comprise additional components such as release agents.Suitable release agents are water soluble and aid in lens deblocking.

It is generally necessary to add one or more cross-linking agents, alsoreferred to as cross-linking monomers, to the reaction mixture, such asethylene glycol dimethacrylate (“EGDMA”), trimethylolpropanetrimethacrylate (“TMPTMA”), glycerol trimethacrylate, polyethyleneglycol dimethacrylate (wherein the polyethylene glycol preferably has amolecular weight up to, e.g., about 5000), and other polyacrylate andpolymethacrylate esters, such as the end-capped polyoxyethylene polyolsdescribed above containing two or more terminal methacrylate moieties.The cross-linking agents are used in the usual amounts, e.g., from about0.000415 to about 0.0156 mole per 100 grams of reactive components inthe reaction mixture. (The reactive components are everything in thereaction mixture except the diluent and any additional processing aidswhich do not become part of the structure of the polymer.)Alternatively, if the hydrophilic monomers and/or thesilicone-containing monomers act as the cross-linking agent, theaddition of a crosslinking agent to the reaction mixture is optional.Examples of hydrophilic monomers which can act as the crosslinking agentand when present do not require the addition of an additionalcrosslinking agent to the reaction mixture include polyoxyethylenepolyols described above containing two or more terminal methacrylatemoieties.

An example of a silicone-containing monomer which can act as acrosslinking agent and, when present, does not require the addition of acrosslinking monomer to the reaction mixture includesα,ω-bismethacryloxypropyl polydimethylsiloxane.

The reaction mixture may contain additional components such as, but notlimited to, UV absorbers, medicinal agents, antimicrobial compounds,reactive tints, pigments, copolymerizable and nonpolymerizable dyes,release agents and combinations thereof.

A polymerization catalyst or initiator is preferably included in thereaction mixture. The polymerization initiators includes compounds suchas lauryl peroxide, benzoyl peroxide, isopropyl percarbonate,azobisisobutyronitrile, and the like, that generate free radicals atmoderately elevated temperatures, and photoinitiator systems such asaromatic alpha-hydroxy ketones, alkoxyoxybenzoins, acetophenones,acylphosphine oxides, bisacylphosphine oxides, and a tertiary amine plusa diketone, mixtures thereof and the like. Illustrative examples ofphotoinitiators are 1-hydroxycyclohexyl phenyl ketone,2-hydroxy-2-methyl-1-phenyl-propan-1-one,bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide(DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenyl phosphineoxide (Irgacure819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide and2,4,6-trimethylbenzoyl diphenylphosphine oxide, benzoin methyl ether anda combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.Commercially available visible light initiator systems include Irgacure819, Irgacure 1700, Irgacure 1800, frgacure 819, Irgacure 1850 (all fromCiba Specialty Chemicals) and Lucirin TPO initiator (available fromBASF). Commercially available UV photoinitiators include Darocur 1173and Darocur 2959 (Ciba Specialty Chemicals). These and otherphotoinitators which may be used are disclosed in Volume III,Photoinitiators for Free Radical Cationic & Anionic Photopolymerization,2^(nd) Edition by J. V. Crivello & K. Dietliker; edited by G. Bradley;John Wiley and Sons; New York; 1998, which is incorporated herein byreference. The initiator is used in the reaction mixture in effectiveamounts to initiate photopolymerization of the reaction mixture, e.g.,from about 0.1 to about 2 parts by weight per 100 parts of reactivemonomer. Polymerization of the reaction mixture can be initiated usingthe appropriate choice of heat or visible or ultraviolet light or othermeans depending on the polymerization initiator used. Alternatively,initiation can be conducted without a photoinitiator using, for example,e-beam. However, when a photoinitiator is used, the preferred initiatorsare bisacylphosphine oxides, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure 819®) or a combination of 1-hydroxycyclohexylphenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO), and the preferred method of polymerizationinitiation is visible light. The most preferred isbis(2,4,6-trimethylbenzoyl)-phenyl phosphine oxide (Irgacure 819®).

The invention further comprises, consists and consists essentially of asilicone hydrogel containing a covalently attached reactive,hydrophilic, polymeric IWA and biomedical device, ophthalmic device andcontact lenses formed from the formulations shown below: (all numbersare preceded by the word “about”) Wt % RHPIWA OPC HM CC 1-15 5-75, or5-60, 0-70, or 5-60, 0-90, or 10-80, or 10-50 or 10-50 or 20-50 3-155-75, or 5-60, 0-70, or 5-60, 0-90, or 10-80, or 10-50 or 10-50 or 20-505-12 5-75, or 5-60, 0-70, or 5-60, 0-90, or 10-80, or 10-50 or 10-50 or20-50RHPIWA is reactive, hydrophilic polymeric internal wetting agentOPC is oxygen permeable componentHM is hydrophilic monomerCC is compatibilizing component

The reaction mixtures of the present invention can be formed by any ofthe methods know to those skilled in the art, such as shaking orstirring, and used to form polymeric articles or devices by knownmethods.

For example, the biomedical devices of the invention may be prepared bymixing reactive components and the diluent(s) with a polymerizationinitator and curing by appropriate conditions to form a product that canbe subsequently formed into the appropriate shape by lathing, cuttingand the like. Alternatively, the reaction mixture may be placed in amold and subsequently cured into the appropriate article.

Various processes are known for processing the reaction mixture in theproduction of contact lenses, including spincasting and static casting.Spincasting methods are disclosed in U.S. Pat. Nos. 3,408,429 and3,660,545, and static casting methods are disclosed in U.S. Pat. Nos.4,113,224 and 4,197,266. The preferred method for producing contactlenses comprising the polymer of this invention is by the molding of thesilicone hydrogels, which is economical, and enables precise controlover the final shape of the hydrated lens. For this method, the reactionmixture is placed in a mold having the shape of the final desiredsilicone hydrogel, i.e., water-swollen polymer, and the reaction mixtureis subjected to conditions whereby the monomers polymerize, to therebyproduce a polymer/diluent mixture in the shape of the final desiredproduct. Then, this polymer/diluent mixture is treated with a solvent toremove the diluent and ultimately replace it with water, producing asilicone hydrogel having a final size and shape which are quite similarto the size and shape of the original molded polymer/diluent article.This method can be used to form contact lenses and is further describedin U.S. Pat. Nos. 4,495,313; 4,680,336; 4,889,664; and 5,039,459,incorporated herein by reference.

The biomedical devices, and particularly ophthalmic lenses of thepresent invention have a balance of properties which makes themparticularly useful. Such properties include clarity, water content,oxygen permeability and contact angle. Thus, in one embodiment, thebiomedical devices are contact lenses having a water content of greaterthan about 17%, preferably greater than about 20% and more preferablygreater than about 25%.

As used herein clarity means substantially free from visible haze.Preferably clear lenses have a haze value of less than about 150%, morepreferably less than about 100%.

Suitable oxygen permeabilities are preferably greater than about 40barrer and more preferably greater than about 60 barrer.

Also, the biomedical devices, and particularly ophthalmic devices andcontact lenses have contact angles (advancing) which are less than about80°, preferably less than about 70° and more preferably less than about65°. In some preferred embodiments the articles of the present inventionhave combinations of the above described oxygen permeability, watercontent and contact angle. All combinations of the above ranges aredeemed to be within the present invention. The non-limiting examplesbelow further describe this invention.

The dynamic contact angle or DCA, was measured at 23° C., with boratebuffered saline, using a Wilhelmy balance. The wetting force between thelens surface and borate buffered saline is measured using a Wilhelmymicrobalance while the sample strip cut from the center portion of thelens is being immersed into the saline at a rate of 100 microns/sec. Thefollowing equation is usedF=2γpcosθ or θ=cos⁻¹(F/2γp)where F is the wetting force, γ is the surface tension of the probeliquid, p is the perimeter of the sample at the meniscus and 0 is thecontact angle. Typically, two contact angles are obtained from a dynamicwetting experiment—advancing contact angle and receding contact angle.Advancing contact angle is obtained from the portion of the wettingexperiment where the sample is being immersed into the probe liquid, andthese are the values reported herein. At least four lenses of eachcomposition are measured and the average is reported.

The water content was measured as follows: lenses to be tested wereallowed to sit in packing solution for 24 hours. Each of three test lenswere removed from packing solution using a sponge tipped swab and placedon blotting wipes which have been dampened with packing solution. Bothsides of the lens were contacted with the wipe. Using tweezers, the testlens were placed in a weighing pan and weighed. The two more sets ofsamples were prepared and weighed as above. The pan was weighed threetimes and the average is the wet weight.

The dry weight was measured by placing the sample pans in a vacuum ovenwhich has been preheated to 60° C. for 30 minutes. Vacuum was applieduntil at least 0.4 inches Hg is attained. The vacuum valve and pump wereturned off and the lenses were dried for four hours. The purge valve wasopened and the oven was allowed reach atmospheric pressure. The panswere removed and weighed. The water content was calculated as follows:$\begin{matrix}{{{Wet}\quad{weight}} = {{{combined}\quad{wet}\quad{weight}\quad{of}\quad{pan}\quad{and}\quad{lenses}} -}} \\{{weight}\quad{of}\quad{weighing}\quad{pan}} \\{{{Dry}\quad{weight}} = {{{combined}\quad{dry}\quad{weight}\quad{of}\quad{pan}\quad{and}\quad{lens}} -}} \\{{weight}\quad{of}\quad{weighing}\quad{pan}} \\{{\%\quad{water}\quad{content}} = {\frac{\left( {{{wet}\quad{weight}} - {{dry}\quad{weight}}} \right)}{{wet}\quad{weight}} \times 100}}\end{matrix}$The average and standard deviation of the water content are calculatedfor the samples are reported.

Modulus was measured by using the crosshead of a constant rate ofmovement type tensile testing machine equipped with a load cell that islowered to the initial gauge height. A suitable testing machine includesan Instron model 1122. A dog-bone shaped sample having a 0.522 inchlength, 0.276 inch “ear” width and 0.213 inch “neck” width was loadedinto the grips and elongated at a constant rate of strain of 2 in/min.until it broke. The initial gauge length of the sample (Lo) and samplelength at break (Lf) were measured. Twelve specimens of each compositionwere measured and the average is reported. Tensile modulus was measuredat the initial linear portion of the stress/strain curve.

Haze is measured by placing a hydrated test lens in borate bufferedsaline in a clear 20×40×10 mm glass cell at ambient temperature above aflat black background, illuminating from below with a fiber optic lamp(Titan Tool Supply Co. fiber optic light with 0.5″ diameter light guideset at a power setting of 4-5.4) at an angle 66° normal to the lenscell, and capturing an image of the lens from above, normal to the lenscell with a video camera (DVC 1300C:19130 RGB camera with Navitar TVZoom 7000 zoom lens) placed 14 mm above the lens platform. Thebackground scatter is subtracted from the scatter of the lens bysubtracting an image of a blank cell using EPIX XCAP V 1.0 software. Thesubtracted scattered light image is quantitatively analyzed, byintegrating over the central 10 mm of the lens, and then comparing to a−1.00 diopter CSI Thin Lens®, which is arbitrarily set at a haze valueof 100, with no lens set as a haze value of 0. Five lenses are analyzedand the results are averaged to generate a haze value as a percentage ofthe standard CSI lens. Oxygen permeability (Dk) may be determined by thepolarographic method generally described in ISO 9913-1:1996(E), but withthe following variations. The measurement is conducted at an environmentcontaining 2.1% oxygen. This environment is created by equipping thetest chamber with nitrogen and air inputs set at the appropriate ratio,for example 1800 ml/min of nitrogen and 200 ml/min of air. The t/Dk iscalculated using the adjusted PO₂. Borate buffered saline was used. Thedark current was measured by using a pure humidified nitrogenenvironment instead of applying MMA lenses. The lenses were not blottedbefore measuring. Four lenses were stacked instead of using lenses ofvaried thickness. A curved sensor was used in place of a flat sensor.The resulting Dk value is reported in barrers.

The following abbreviations are used throughout the Examples and havethe following meanings.

-   SiGMA 2-propenoic acid,    2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disiloxanyl]propoxy]propyl    ester-   DMA N,N-dimethylacrylamide-   HEMA 2-hydroxyethyl methacrylate-   mPDMS 800-1000 MW (Mn) monomethacryloxypropyl terminated    mono-n-butyl terminated polydimethylsiloxane-   Norbloc 2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole-   CGI 1850 1:1 (weight) blend of 1-hydroxycyclohexyl phenyl ketone and    bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide-   CGI 819 2,4,6-trimethylbenzyldiphenyl phosphine oxide-   LMWHP low molecular weight hydrophilic polymer comprised of a    poly(N-vinyl pyrrolidone) backbone with either hydroxyl, amine,    carboxylic acid, or carboxylate end groups-   HMWHC high molecular weight hydrophilic copolymer comprised of    poly(N-vinyl pyrrolidone)-co-(9-vinylcarbazole) (97.5/2.5)-   RHPIWA reactive, hydrophilic polymeric IWA comprised of a    poly(N-vinyl pyrrolidone) backbone with covalently attached    photo-polymerizable end groups-   IPA isopropyl alcohol-   D3O 3,7-dimethyl-3-octanol-   TEGDMA tetraethyleneglycol dimethacrylate-   EGDMA ethyleneglycol dimethacrylate-   MMA methyl methacrylate-   THF tetrahydrofuran-   Dioxane 1,4-dioxane-   DMF N,N-dimethylformamide-   DMAc N,N-dimethylacetamide-   PVP low Poly(N-vinyl pyrrolidone), ˜2500 MW

EXAMPLE 1

9-Vinylcarbazole (0.79 gm, 4.1 mmol) (Aldrich, Milwaukee, Wis.),2,2′-Azobis[N-(2-carboxyethyl)-2-methylpropionamidine]tetrahydrate (0.16gm, 0.46 mmol) (Wako Chemicals USA, St. Louis, Mo.) and freshlydistilled N-vinyl-2-pyrrolidone (NVP) (15.1 gm, 136 mmol) were added toa 250 mL round bottom flask equipped with magnetic stirrer and nitrogeninlet. Methyl alcohol (19.2 gm) and distilled water (23.4 gm) were addedto the reaction mixture. The mixture was degassed using 3freeze-pump-thaw cycles and then allowed to warm to ambient temperature.The reaction mixture was heated at 60° C. for 16 hours, thenprecipitated three times using acetone as asolvent to yield a whitepolymer with Mn, Mw, and polydispersity values of 166,000, 420,000, and2.6, respectively. Molecular weights were measured by gel permeationchromatography (GPC) using poly(2-vinylpyridine) standards andhexafluoroisopropanol as mobile phase. ¹H NMR (D₂O):

=7.0-8.2 (bm, 8H, carbazole aromatic H), 3.4-3.8 (bm, 1H, —CH₂CH—),2.8-3.3 (bm, 2H, —C[O]NCH₂—), 2.0-2.4 (bm, 2H, —C[O]CH₂—), 1.8-2.0 (bm,2H, —CH₂CH₂CH₂—), 1.4-1.7 (bm, 2H, —CH₂CH—).

EXAMPLE 2

9-Vinylcarbazole (Aldrich, Milwaukee, Wis.) (1.9 gm, 9.6 mmol),2,2′-azobis[N-(2-carboxyethyl)-2-methylpropionamidine]tetrahydrate (WakoChemicals USA, St. Louis, Mo.) (0.56 gm, 1.4 mmol) and freshly distilledN-vinyl-2-pyrrolidone (NVP) (52.8 gm, 475 mmol) were added to a 1 Lround bottom flask equipped with magnetic stirrer and nitrogen inlet.Methyl alcohol (231.4 gm) was added to the reaction mixture. The mixturewas degassed using 3 freeze-pump-thaw cycles and then allowed to warm toambient temperature. The reaction mixture was heated at 60° C. for 4hours, then isolated by precipitation (3 times) into diisopropyl etherto yield a white polymer with Mn, Mw, and polydispersity values of30,000, 110,000, and 3.7, respectively, using poly(2-vinylpyridine)standards and hexafluoroisopropanol as mobile phase.

EXAMPLE 3

Polymer from Example 2 (27.0 gm, 239 mmol), DMAC (173 gm),4-dimethylaminopyridine (DMAP, Avocado Research Chemicals, Heysham,England) (1.2 gm, 9.6 mmol), pyridine (20 mL), methacrylic anhydride(Aldrich, Milwaukee, Wis.) (7.43 g, 48.2 mmol) and hydroquinone (50 mg,0.5 mmol, Aldrich, Milwaukee, Wis.) were charged to a 500 mL roundbottom flask equipped with magnetic stirrer and nitrogen inlet. Thereaction mixture was heated at 70° C. for 6 hours and then isolated byprecipitation into diisopropyl ether (three times) to afford a whitesolid with Mn, Mw, and polydispersity values of 33,000, 109,000, and3.3, respectively, using poly(2-vinylpyridine) standards andhexafluoroisopropanol as mobile phase.

EXAMPLE 4

N-vinylpyrrolidone (50.0 gm, 450 mmol), 2-mercaptopropionic acid(Aldrich, Milwaukee, Wis.) (0.97 g, 9.2 mmol), 9-vinylcarbazole (1.8 g,9.2 mmol), and2,2′-azobis[N-(2-carboxyethyl)-2-methylpropionamidine]tetrahydrate (WakoChemicals USA, St. Louis, Mo.) (0.53 gm, 1.3 mmol), DMAC (143 gm), anddistilled water (40 mL) were charged to a 500 mL round bottom flaskequipped with a nitrogen inlet and magnetic stirrer. The reactionmixture was frozen using an external CO₂/acetone bath and then placedunder vacuum. The solution was backfilled with nitrogen, thawed, andfrozen again under vacuum for a total of 3 freeze-pump-thaw cycles. Thesolution was heated to 60° C. under nitrogen for 6 hours. Hydroquinone(50 mg, 0.5 mmol, Aldrich, Milwaukee, Wis.) was added to the reactionmixture, which was then cooled to 5° C. 1-Hydroxybenzotriazole (Aldrich,Milwaukee, Wis.) (3.7 gm, 28 mmol), 2-aminoethyl methacrylatehydrochloride (Aldrich, Milwaukee, Wis.) (4.6 gm, 28 mmol), and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC)(Aldrich, Milwaukee, Wis.) (5.3 gm, 28 mmol) were added and the mixturewas stirred for 1 hour at 5° C., followed by an additional 20 hours atroom temperature. The reaction mixture was diluted with DMAC (250 mL)and then poured slowly into 70:30 t-butyl methyl ether/hexanes toprecipitate out the white solid (90 percent). The polymer was dissolvedin 2-propanol and re-precipitated an additional 2 times. The resultantPVP macromer had Mn, Mw, and polydispersity values of 41,000, 155,000,and 3.7, respectively.

EXAMPLE 5

N-vinylpyrrolidone (42.6 gm, 384 mmol), 9-vinylcarbazole (0.59 gm, 3.0mmol), 2,2′-azobis{2-[1-(2-hydroxyethyl)-2-imidazolin-2-yl]propane)dihydrochloride (WakoChemicals USA, St. Louis, Mo.) (2.67 gm, 7.89 mmol), and methyl alcohol(160 gm) were charged to a 500 mL round bottom flask equipped with anitrogen inlet and magnetic stirrer. The reaction mixture was subjectedto 3 freeze-pump-thaw cycles and then heated to 60° C. under nitrogenfor 6 hours. The polymer was isolated as a white solid (85 percent) byprecipitation into diisopropyl ether 3 times and then dried.

The resultant polymer (15.8 gm, 141 mmol) was dissolved in anhydrous1,4-dioxane (Aldrich, Milwaukee, Wis.) (400 mL). Hydroquinone (50 mg,0.5 mmol) was added to the reaction mixture, followed by2-isocyanatoethyl methacrylate (Aldrich, Milwaukee, Wis.) (2.2 gm, 14mmol) and 100 microL of 0.33M stannous octoate (made by dissolvingstannous octoate (Aldrich, Milwaukee, Wis.) in anhydrous toluene). Thereaction mixture was heated to 70° C. for 8 hours and then poured slowlyinto diisopropyl ether to yield a white solid (88 percent). The polymerwas re-dissolved in 2-propanol and precipitated 2 additional times. Theresultant PVP macromer had Mn, Mw, and polydispersity values of 8,000,46,000, and 6.0, respectively.

EXAMPLE 6

N-vinylpyrrolidone (50.4 gm, 453 mmol), 2-mercaptopropionic acid(Aldrich, Milwaukee, Wis.) (1.0 gm, 9.2 mmol), 9-vinylcarbazole (1.78gm, 9.4 mmol), and 2,2′-azobis(2-methylpropionamide)dihydrochloride(Wako Chemicals USA, St. Louis, Mo.) (2.5 gm, 9.3 mmol), DMAC (150 gm),and distilled water (100 mL) were charged to a 500 mL round bottom flaskequipped with a nitrogen inlet and magnetic stirrer. The reactionmixture was frozen using an external CO₂/acetone bath and then placedunder vacuum. The solution was backfilled with nitrogen, thawed, andfrozen again under vacuum for a total of 3 freeze-pump-thaw cycles. Thesolution was heated to 60° C. under nitrogen for 6 hours. Hydroquinone(50 mg, 0.5 mmol) was added to the reaction mixture, which was thencooled to 10° C. 1-Hydroxybenzotriazole (3.9 gm, 30 mmol), 2-aminoethylmethacrylate hydrochloride (4.6 gm, 28 mmol), and EDC (5.7 gm, 30 mmol)were added and the mixture was stirred for 1 hour at 5° C., followed byan additional 40 hours at room temperature. The reaction mixture wasdiluted with DMAC (200 mL) and then poured slowly into 70:30 t-butylmethyl ether/hexanes to precipitate out the white solid (84 percent).

The polymer was dissolved in 2-propanol and re-precipitated anadditional 2 times.

The resultant PVP macromer had Mn, Mw, and polydispersity values of9,800, 44,000, and 4.5, respectively.

EXAMPLE 7 Contact Lens Formation

The reaction components and diluent (tert-amyl alcohol) listed in Table2 were mixed together with stirring, shaking, or rolling for at leastabout 3 hours at 23° C., until all components were dissolved. Thereactive components are reported as weight percent of all reactivecomponents and the diluent and low molecular weight PVP (PVP low) areweight percents of reaction mixture.

The reactive components were purged for approximately 15 minutes usingN₂. Approximately 40-50 microliters of the reaction formulations werepipetted onto clean polypropylene concave mold halves and covered withthe complementary polypropylene convex mold halves. The mold halves werecompressed and the mixtures were cured at 55° C. for about 30 minutes inthe presence of visible light (0.4 mW/cm² using Philips TL 20W/03Tfluorescent bulbs, as measured by an International Lightradiometer/photometer). The molds were allowed to cool to roomtemperature. The top mold halves were removed and the lenses gentlyremoved using tweezers. The lenses were released in water at 90° C. forabout 20 minutes and then placed in vials containing borate bufferedpacking solution. TABLE 2 Example Component 7A 7B 7C 7D 7E 7F SiGMA 30.530.5 30.5 30.5 30 30 Ex 1 6.1 0 0 0 0 0 Ex 2 0 6.1 0 0 0 0 Ex 3 0 0 6.10 0 0 Ex 4 0 0 0 6.1 0 0 Ex 5 0 0 0 0 6 0 Ex 6 0 0 0 0 0 6 DMA 31.5 31.531.5 31.5 31 31 mPDMS 22.3 22.3 22.3 22.3 22 22 HEMA 8.6 8.6 8.6 8.6 8.58.5 Norbloc 0 0 0 0 1.5 1.5 CGI 1850 0 0 0 0 0 0 CGI 819 0.23 0.23 0.230.23 0.23 0.23 TEGDMA 0 0 0 0 0 0 EGDMA 0.76 0.76 0.76 0.76 0.75 0.75PVP low 11 11 11 11 11 11 t-amyl 29 29 29 29 29 29 alcohol percent

The reactive, hydrophilic polymeric IWAs (RHPIWA) were synthesized inthe presence of small amounts (˜1 mol percent) of fluorescent vinylmonomers. Covalently attached fluorescent “probes”, or fluorophores,were used to detect the diffusion of unreacted monomers from theproduction of the reactive, hydrophilic polymeric IWAs from the contactlenses. The concentration of fluorescent probe in the RHPIWA is lowenough so that the physical properties of the labeled RHPIWA are similarto that of unlabeled RHPIWA.

The fluorescent probes and fluorescently labeled macromers were firsttested to determine whether conditions necessary to make lenses, such asfor example, light intensity and heat, affect the emission offluorescence of the fluorophore. The resultant fluorescently labeledmacromers were then combined with reactive components and diluents tomake contact lenses. The release of PVP macromers labeled withfluorescent carbazole groups was measured from the extraction mediausing a Shimadzu RF5301-PC spectrofluorometer (excitation λ=343 nm,emission λ=348 nm, slit width=3 nm). A standard calibration curve of PVPmacromer standards was used to correlate the amount of PVP macromerrelease from lenses. As a control, a high molecular weight hydrophiliccopolymer (HMWHC) was used based on PVP (containing 2.5 mol percentcarbazole groups) with Mn, Mw, and PD values of 94,800, 511,000, and5.4, respectively. The molecular weight of the internal wetting agent(Mn), and amount of internal wetting agent extracted after 50-100 hrsare shown in Table 3. TABLE 3 Ex. # 7A 7B 7C 7D 7E 7F M_(n) 166,00030,000 33,000 41,000 8,000 9,800 Extraction Time (hrs) 100 104 96 52 10299 Internal wetting agent 420 110 109 155 46 44 M_(w) × 10⁻³ (PDI) (2.6)(3.7) (3.3) (3.7) (6.0) (4.5) Percent wetting agent released 12 50 35 525 20

The results of Examples 7A through 7F show that the reaction mixturecomponents and their amounts may be varied. All lenses showed low haze.

The reactive, hydrophilic polymeric internal wetting agents in Examples7C through 7F) were comparable or lower in molecular weight than the lowmolecular weight hydrophilic polymer of Example 2 (used in formulation7B) having no photo-polymerizable groups. The percent release of thereactive, hydrophilic polymeric IWAs (Examples 7C-F) from contact lenseswas lower (5-35%) as compared to polymers without photo-polymerizablegroups (Example 7B, 50%). Example 7A used a non-reactive high molecularweight hydrophilic copolymers. FIG. 1 shows the percent of internalwetting agent loss in IPA as a function of time. Example 7D, whichcomprises a reactive, hydrophilic polymeric IWA lost less than about 5%of the IWA, while Example 7A (which contained a non-reactivehydrophilic, polymeric IWA) lost about 12% of the IWA. Based on Example4, comparable and even slower release rates can be achieved using lowermolecular hydrophilic polymeric IWAs with photo-polymerizable endgroup(s).

The Examples also show that reactive, hydrophilic polymeric IWAs may besynthesized using several synthetic routes, and resulting in resultingin reactive, hydrophilic polymeric IWAs with different structures,particularly at the end groups.

The lenses from Example 7F were analyzed to determine contact angle,water content and mechanical properties. The results are shown in Table4, below. TABLE 4 Advancing contact angle 52° Water content 45.2%Modulus 110 psi Elongation at break  124%

Thus the reactive, hydrophilic polymeric IWAs produce contact lenseswith desirable properties.

EXAMPLE 8

Reactive, hydrophilic polymeric IWA was synthesized as in Example 3,except without the use of 9-vinylcarbazole to yield a white polymer withMn, Mw, and polydispersity values of 38,000, 113,000, and 3.0,respectively.

EXAMPLE 9

Reactive, hydrophilic polymeric IWA was synthesized as in Example 4,except without the use of 9-vinylcarbazole to yield a white polymer withMn, Mw, and polydispersity values of 34,500, 138,000, and 4.0,respectively.

EXAMPLE 10

Reactive, hydrophilic polymeric IWA was synthesized as in Example 5,except without the use of 9-vinylcarbazole to yield a white polymer withMn, Mw, and polydispersity values of 8,500, 42,000, and 4.9,respectively.

EXAMPLE 11

Reactive, hydrophilic polymeric IWA was synthesized as in Example 6,except without the use of 9-vinylcarbazole to yield a white polymer withMn, Mw, and polydispersity values of 10,000, 40,000, and 4.0,respectively.

EXAMPLE 12 Contact Lens Formation

Lenses containing the reactive, hydrophilic polymeric internal wettingagents of Examples 8-11 (no fluorophore) were made as in Example 7. Thecure intensity, temperature, and time were maintained 4.0 mW/cm², 55°C., and 12 minutes, respectively. Again, low haze was observed in alllenses.

EXAMPLE 13

NVP (50.5 gm, 454 mmol), vinyl acetate (6.7 gm, 78 mmol),9-Vinylcarbazole (1.0 gm, 5.4 mmol),2,2′-Azobis[N-(2-carboxyethyl)-2-methylpropionamidine]tetrahydrate(0.578 gm, 1.39 mmol), methyl alcohol (170 gm), and distilled water (27gm) were added to a 500 mL round bottom flask equipped with magneticstirrer and nitrogen inlet. The mixture was degassed using 3freeze-pump-thaw cycles and then allowed to warm to ambient temperature.The reaction mixture was heated at 60° C. for 6 hours, and then isolatedby precipitation (3 times) into diisopropyl ether to yield a whitepolymer. The polymer was redissolved in distilled water (1 L) and NaOHwas added (3.6 gm, 89 mmol). The reaction mixture was heated to 70° C.for 4 hours and then concentrated by rotary evaporation of the solvent.The polymer was precipitated from cold acetone, redissolved in 2 Ldistilled water, and dialyzed for 72 hours against water and 48 hoursagainst isopropyl alcohol using 3500 molecular weight cut-offSpectra/Por® dialysis membrane (purchased from VWR). The polymer wasisolated by removal of solvent to yield an off-white solid with Mn, Mw,and polydispersity values of 49,000, 191,000, and 3.9, respectively.

EXAMPLE 14

The high molecular weight polymer product from Example 13 (21 gm, 200mmol), anhydrous triethylamine (11.6 gm, 115 mmol),4-(dimethylamino)pyridine (Aldrich, Milwaukee, Wis.) (6.1 gm, 50 mmol),hydroquinone (Aldrich, Milwaukee, Wis.) (50 mg, 0.5 mmol) and anhydrous1,4-dioxane (300 mL) were charged to a 500 mL round bottom flaskequipped with a nitrogen inlet and magnetic stirrer. Methacryloylchloride (Aldrich, Milwaukee, Wis.) (6.0 gm, 57 mmol) was added dropwiseto the reaction mixture. The mixture was subsequently heated at 60° C.for 4 hours. The polymer was isolated by precipitation into 50/50t-butyl methyl ether/hexanes to yield an off-white solid with Mn, Mw,and polydispersity values of 54,000, 200,000, and 3.7, respectively.

EXAMPLE 15

NVP (50.7 gm, 457 mmol), vinyl acetate (3.7 gm, 43 mmol),9-vinylcarbazole (0.90 gm, 4.9 mmol),2,2′-Azobis[N-(2-carboxyethyl)-2-methylpropionamidine]tetrahydrate (0.38gm, 0.91 mmol), methyl alcohol (75 gm), and distilled water (75 gm) wereadded to a 500 mL round bottom flask equipped with magnetic stirrer andnitrogen inlet. The mixture was degassed using 3 freeze-pump-thaw cyclesand then allowed to warm to ambient temperature. The reaction mixturewas heated at 60° C. for 18 hours, and then isolated by precipitation (3times) into 50/50 diisopropyl ether/hexanes to yield a white polymer.The polymer was redissolved in distilled water (1 L) and NaOH was added(1.7 gm, 43 mmol). The reaction mixture was heated to 60° C. for 6 hoursand then concentrated by rotary evaporation of the solvent at 60° C. Thepolymer was precipitated from 70/30 acetone/hexanes, redissolved in 2 Ldistilled water, and dialyzed for 72 hours against water and 48 hoursagainst isopropyl alcohol using 3500 molecular weight cut-offSpectra/Por® dialysis membrane (purchased from VWR). The polymer wasisolated by removal of solvent to yield an off-white solid with Mn, Mw,and polydispersity values of 86,000, 310,000, and 3.6, respectively.

EXAMPLE 16

The high molecular weight polymer product from Example 15 (25 gm, 240mmol), hydroquinone (Aldrich, Milwaukee, Wis.) (50 mg, 0.5 mmol),2-isocyanatoethyl methacrylate (Aldrich, Milwaukee, Wis.) (3.21 gm, 20.4mmol) and 100 millililters of 0.33M stannous octoate [made by dissolvingstannous octoate (Aldrich, Milwaukee, Wis.) in anhydrous toluene], andanhydrous 1,4-dioxane (300 mL) were charged to a 500 mL round bottomflask equipped with a nitrogen inlet and magnetic stirrer. The reactionmixture was heated to 70° C. for 8 hours and then poured slowly intodiisopropyl ether to yield a white solid (92 percent). The polymer wasdissolved in 2-propanol and precipitated 2 additional times affording anoff-white solid with Mn, Mw, and polydispersity values of 86,000,320,000, and 3.7, respectively.

EXAMPLE 17

The reaction components and diluent (tert-amyl alcohol) listed in Table3 were mixed together and processed to make lenses in accordance withthe procedure described in Example 7, above.

In one embodiment, reactive, hydrophilic polymeric IWAs were synthesizedin the presence of small amounts (˜1 mol percent) of fluorescent vinylmonomers. The general structure is shown in Formulae XIX, where9-vinylcarbazole units are present between 0.1 and 2 mol percent.

Small amounts of covalently attached fluorescent “probes”, orfluorophores, were used to detect the diffusion of the polymers listedin Table 3 from contact lenses, as described in Example 7. The lenscompositions, molecular weight of the internal wetting agent, and amountof internal wetting agent extracted after 50-100 hrs are shown in Table5, below. TABLE 5 17A 17B 17C 17D 17E 17F Component SiGMA 30.5 30.5 30.530.5 30 30 Ex 1 6.1 0 0 0 0 0 Ex 2 0 6.1 0 0 0 0 Ex 13 0 0 6.1 0 0 0 Ex14 0 0 0 6.1 0 0 Ex 15 0 0 0 0 6.1 0 Ex 16 0 0 0 0 0 6.1 DMA 31.5 31.531.5 31.5 31.5 31.5 MPDMS 22.3 22.3 22.3 22.3 22.3 22.3 HEMA 8.6 8.6 8.68.6 8.6 8.6 Norbloc 0 0 0 0 0 0 CGI 819 0.23 0.23 0.23 0.23 0.23 0.23TEGDMA 0 0 0 0 0 0 EGDMA 0.76 0.76 0.76 0.76 0.76 0.76 PVP low 11 11 1111 11 11 t-amyl 29 29 29 29 29 29 alcohol % Percent PVP macromerreleased from lens after extraction in 2-propanol Extraction 100 104 9896 100 99 Time (hrs) IWA M_(w) × 420 110 191 200 310 320 10⁻³ (PDI)(2.6) (3.7) (3.9) (3.7) (3.6) (3.7) Weight % 12 50 26 0.3 18 0.4 releaseof IWA

The results of Examples 17A through F show that the reaction mixturecomponents and their amounts may be varied. All lenses showed low haze.

As shown in Table 5, the rate of release of the polymers withoutreactive groups (Examples 17C and 17E) was faster than that of the highmolecular weight control (Example 17A) and slower than that of the lowmolecular weight control (Example 17B) after ˜100 hours in isopropanol.Examples 17D and 17F, which contained reactive, hydrophilic polymericIWAs of the present invention, displayed insignificant release of theinternal wetting agents. This is significant since preservation of theinternal wetting agent helps maintain lens wettability in addition toother previously described lens properties since the initial weightpercent of components in the reaction mixture remains relativelyconstant after curing and extraction in organic solvents.

EXAMPLE 18

Synthesis was carried out as in Example 13 without the use of9-vinylcarbazole. In addition, methyl alcohol in the reaction mixturewas replaced by an equal weight of distilled water. Polymer Mn, Mw, andpolydispersity was: 45,000, 225,000, and 5.0.

EXAMPLE 19

Synthesis was carried out as in Example 14 without the use of9-vinylcarbazole. In addition, methyl alcohol in the reaction mixturewas replaced by an equal weight of distilled water. Polymer Mn, Mw, andpolydispersity were: 49,000, 230,000, and 4.7.

EXAMPLES 20

Lenses containing the low molecular weight hydrophilic polymer ofExample 18 and the reactive, hydrophilic polymer IWA of Example 19 weremade as in Example 17 using similar amounts of reaction components, butwithout the addition of fluorophore. The cure intensity, temperature,and time were similarly held at 4.0 mW/cm², 55° C., and 12 minutes,respectively. Low haze was observed in all lenses.

1. A silicone hydrogel formed from a reaction mixture comprising atleast one oxygen permeable component and at least one reactive,hydrophilic polymeric internal wetting agent.
 2. The hydrogel of claim 1wherein said internal wetting agent has a Mw of about 5,000 to about2,000,000 Daltons.
 3. The hydrogel of claim 1 wherein said internalwetting agent has a Mw of about 5,000 to about 180,000 Daltons.
 4. Thehydrogel of claim 1 wherein said internal wetting agent has a Mw ofabout 5,000 to about 150,000 Daltons.
 5. The hydrogel of claim 1 whereinsaid internal wetting agent has a Mw of about 60,000 to about 2,000,000Daltons.
 6. The hydrogel of claim 1 wherein said internal wetting agenthas a Mw of about 1800,000 to about 1,500,000 Daltons
 7. The hydrogel ofclaim 1 comprising a mixture of reactive, hydrophilic polymeric IWAs. 8.The hydrogel of claim 1 wherein said internal wetting agent is derivedfrom at least one polymer selected from the group consisting ofpolyamides, polylactones, polyimides, polylactams and functionalizedpolyamides, polylactones, polyimides, polylactams and copolymers andmixtures thereof.
 9. The hydrogel of claim 1 wherein said internalwetting agent is derived from at least one polymer selected from thegroup consisting of polymers of Formulae of II, IV, VI and VII


10. The hydrogel of claim 1 wherein said internal wetting agent isderived from at least one polymer comprising repeating units of FormulaVIII

wherein Q is a direct bond,

wherein R^(c) is a C1 to C3 alkyl group; R^(a) is selected from H,straight or branched, substituted or unsubstituted C1 to C4 alkylgroups, R^(b) is selected from H, straight or branched, substituted orunsubstituted C1 to C4 alkyl groups, amino groups having up to twocarbons, amide groups having up to 4 carbon atoms and alkoxy groupshaving up to two carbons and wherein the number of carbon atoms in R^(a)and R^(b) taken together is 8, preferably 6 or less. As used hereinsubstituted alkyl groups include alkyl groups substituted with an amine,amide, ether or carboxy group.
 11. The hydrogel of claim 1 wherein saidreactive, hydrophilic polymeric internal wetting agent is present in anamounts from about 1 to about 15 weight percent, based upon total weightof all reactive components.
 12. The hydrogel of claim 1 wherein saidinternal wetting agent is present in an amounts from about 3 to about 15percent, based upon total weight of all reactive components.
 13. Thehydrogel of claim 1 wherein said internal wetting agent is present in anamounts from about 5 to about 12 percent, based upon total weight of allreactive components.
 14. The hydrogel of claim 10 wherein said internalwetting agent further comprises repeating units selected from the groupconsisting of N-vinylpyrrolidone, N,N-dimethylacrylamide,2-hydroxyethylmethacrylate, vinyl acetate, acrylonitrile, methylmethacrylate, siloxane substituted acrylates or methacrylates, alkyl(meth)acrylates and mixtures thereof.
 15. The hydrogel of claim 10wherein said internal wetting agent further comprises repeating unitsselected from the group consisting of N-vinylpyrrolidone,N,N-dimethylacrylamide, 2-hydroxyethylmethacrylate and mixtures thereof.16. The hydrogel of claim 10 wherein said repeating unit comprisesN-vinyl-N-methylacetamide.
 17. The hydrogel of claim 1 wherein saidoxygen permeable component comprises at least one silicone containingcomponent.
 18. The hydrogel of claim 17 wherein said at least onesilicone containing component is selected from the group consisting ofsilicone containing monomers, silicone containing macromers and mixturesthereof.
 19. The hydrogel of claim 17 wherein said at least one siliconecontaining component is selected from the group consisting ofpolysiloxyalkyl(meth)acrylic monomers, poly(organosiloxane) prepolymers,silicone containing vinyl carbonate monomers, silicone containing vinylcarbamate monomers, and mixtures thereof.
 20. The hydrogel of claim 1further comprising at least one hydrophilic monomer.
 21. The hydrogel ofclaim 20 wherein said hydrophilic monomer is present in amounts up toabout 60 weight % based upon weight of all reactive components.
 22. Thehydrogel of claim 20 wherein said hydrophilic monomer is present inamounts between about 10 to about 60 weight %, based upon weight of allreactive components.
 23. The hydrogel of claim 20 wherein saidhydrophilic monomer is present in amounts between about 20 to about 40weight %, based upon weight of all reactive components.
 24. The hydrogelof claim 20 wherein said hydrophilic monomer is selected from the groupconsisting of N,N-dimethyl acrylamide (DMA), 2-hydroxyethyl acrylate,2-hydroxyethyl methacrylate, glycerol methacrylate, 2-hydroxyethylmethacrylamide, N-vinylpyrrolidone, polyethyleneglycol monomethacrylate,and mixtures thereof.
 25. The hydrogel of claim 1 further comprising atleast one compatibilizing component.
 26. The hydrogel of claim 25wherein said compatibilizing component is selected from hydroxylcontaining monomers and macromers.
 27. The hydrogel of claim 25 whereinsaid compatibilizing component is selected from the group consisting of2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxyethylmethacrylamide, 2-hydroxyethyl acrylamide, N-2-hydroxyethyl vinylcarbamate, 2-hydroxyethyl vinyl carbonate, 2-hydroxypropyl methacrylate,hydroxyhexyl methacrylate, hydroxyoctyl methacrylate and hydroxylfunctional monomers comprising silicone or siloxane groups and mixturesthereof.
 28. The hydrogel of claim 25 wherein said compatibilizingcomponent is selected from the group consisting of 2-hydroxyethylmethacrylate,3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane,3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane,bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane,3-methacryloxy-2-(2-hydroxyethoxy)propyloxy)propylbis(trimethylsiloxy)methylsilane,N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate andN,N,N′,N′-tetrakis(3-methacryloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxaneand mixtures thereof.
 29. The hydrogel of claim 25 wherein saidcompatibilizing component is selected from the group consisting of2-hydroxyethyl methacrylate,3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane),3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane andmixtures thereof.
 30. The hydrogel of claim 25 wherein saidcompatibilizing component is present in amounts between about 5 to about90 weight percent, based on total weight of the reactive components. 31.The hydrogel of claim 25 wherein said compatibilizing component ispresent in amounts between about 10 to about 80 weight percent based ontotal weight of the reactive components.
 32. The hydrogel of claim 25wherein said compatibilizing component is present in amounts betweenabout 20 to about 50 weight percent, based on total weight of thereactive components.
 33. A contact lens formed from the hydrogel ofclaim
 1. 34. The hydrogel of claim 1 wherein said reactive, hydrophilicpolymeric IWA comprises a reactive high molecular weight copolymerderived from monomers comprising vinyllactam monomers and vinylcarboxylate monomers.
 35. The hydrogel of claim 34 wherein saidreactive, hydrophilic polymeric IWA has a molecular weight (weightaverage) of at least about 60,000 Daltons.
 36. The hydrogel of claim 34wherein said reactive, hydrophilic polymeric IWA has a molecular weight(weight average) of between about 60,000 to about 750,000 Daltons. 37.The hydrogel of claim 34 wherein said reactive, hydrophilic polymericIWA has a molecular weights (weight average) of between about 180,000 toabout 500,000 Daltons.
 38. The hydrogel of claim 34 wherein saidvinyllactams monomers are selected from the group consisting ofN-vinyl-2-pyrrolidone, N-vinyl-2-piperidone, N-vinyl-2-caprolactam,N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-3-methyl-2-piperidone,N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-pyrrolidone,N-vinyl-4-methyl-2-caprolactam, N-vinyl-5-methyl-2-pyrrolidone,N-vinyl-5-methyl-2-piperidone, N-vinyl-5,5-dimethyl-2-pyrrolidone,N-vinyl-3,3,5-trimethyl-2-pyrrolidone,N-vinyl-5-methyl-5-ethyl-2-pyrrolidone,N-vinyl-3,4,5-trimethyl-3-ethyl-2-pyrrolidone,N-vinyl-6-methyl-2-piperidone, N-vinyl-6-ethyl-2-piperidone,N-vinyl-3,5-dimethyl-2-piperidone, N-vinyl-4,4-dimethyl-2-piperidone,N-vinyl-7-methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam,N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl4,6-dimethyl-2-caprolactam,N-vinyl-3,5,7-trimethyl-2-caprolactam, N-vinylmaleimide,vinylsuccinimide and mixtures thereof.
 39. The hydrogel of claim 34wherein said vinyllactam monomers are selected from the group consistingof heterocyclic monomers containing 4 carbon atoms in the heterocyclicring.
 40. The hydrogel of claim 34 wherein said vinyllactams monomercomprises N-vinyl-2-pyrrolidone.
 41. The hydrogel of claim 34 whereinsaid vinyl carboxylate monomers are selected from the group consistingof compounds having 1 to 10 carbon atoms and both vinyl and carboxylatefunctionality.
 42. The hydrogel of claim 34 wherein said vinylcarboxylate monomers are selected from the group consisting of vinylheptanoate, vinyl hexanoate, vinyl pentanoate, vinyl butanoate, vinylpropanoate (vinyl propionate), vinyl ethanoate (vinyl acetate) andmixtures thereof.
 43. The hydrogel of claim 34 wherein said vinylcarboxylate monomer comprises vinyl acetate.
 44. The hydrogel of claim34, wherein said reactive, hydrophilic polymeric IWA is selected fromthe group consisting of compounds of Formula IX, X

and mixtures thereof.